Although much is understood about the epidemiology and virology of Respiratory Synctial Virus (RSV), three important issues remain unresolved: (l) complete definition of the factors which influence severity of illness, (2) an explanation of the frequency of reinfection, (3) a full understanding of immune mechanisms, and (4) the failure of R vaccines. The long term objectives of this proposal, an extension current grant R01 AI20608-03, are to better define those factors which influence the severity of Respiratory Syncytial Virus (RSV) infection and to quantitate immune parameters which may influence the incidence a severity of infection. New information suggests that clinically relevant strain differences may exist, and have an influence on the issues above. The specific aims of this proposal are to (1) confirm preliminary observations suggesting that severity of RSV infection is close associated with strain type and, (2) to determine whether primary infection with one strain of RSV in the first year of life confers preferential protection against occurance of an severity of reinfection with the same strain in the second year of life. In addition, we will correlate the degree of protection with strain specific immune parameters, specifically humoral IgG and nasal secretory antibody to the envelope glycoproteins of RSV. To achieve the first aim, we propose a case-control study of 2 infants hospitalized with primary RSV infection and 150 infants with mild community based infections (non-hospitalized). Comparative analysis clinical data from these groups should reveal differences in severity related to strain. To achieve the second aim, we will conduct - prospective cohort study of 300 infants who have had primary R infection in which the occurrence, strain, and severity of reinfection would be determined in the second year of life. The information obtained will be applicable to vaccine development and may better define those components of an RSV vaccine necessary for optimal protection.